Stability of Nanopeptides: Structure and Molecular Exchange of Self-assembled Peptide Fibers

Often nanostructures formed by self-assembly of smallmoleculesbased on hydrophobic interactions are rather unstable, causing morphologicalchanges or even dissolution when exposed to changes in aqueous media.In contrast, peptides offer precise control of the nanostructure througha range of molecular interactions where physical stability can beengineered in and, to a certain extent, decoupled from size via rationaldesign. Here, we investigate a family of peptides that form beta-sheetnanofibers and demonstrate a remarkable physical stability even afterattachment of poly(ethylene glycol). We employed small-angle neutron/X-rayscattering, circular dichroism spectroscopy, and molecular dynamicssimulation techniques to investigate the detailed nanostructure, stability,and molecular exchange. The results for the most stable sequence didnot reveal any structural alterations or unimer exchange for temperaturesup to 85 & DEG;C in the biologically relevant pH range. Only undersevere mechanical perturbation (i.e., tip sonication) would the fibersbreak up, which is reflected in a very high activation barrier forunimer exchange of & SIM;320 kJ/mol extracted from simulations.The results give important insight into the relation between molecularstructure and stability of peptide nanostructure that is importantfor, e.g., biomedical applications.